ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

An endogenously formed metabolite of progesterone, 3alpha-hydroxy-5alpha-dihydroprogesterone (3alpha-OH-5alpha-DHP) modulates the gamma-aminobutyric acid receptor complex and plays a physiologic role in brain excitability regulation. On the basis of in vitro observations of 3alpha-OH-5alpha-DHP-enhanced [(3) Hydrogen]flunitrazepam binding, we investigated the potential clinical effect of coadministering oral progesterone and triazolam. Sixteen postmenopausal women were randomly assigned to receive either intravenous triazolam plus oral progesterone 300 mg (TRZPROG) or intravenous triazolam plus oral placebo (TRZ). Triazolam was infused until 0.5 mg was given or until a predetermined maximal response was attained. Pharmacodynamic evaluation included DSST, continuous performance test, hand-eye coordination, short-term memory, and sedation. Effect ratios were calculated as the ratio of area under the effect-time curve to area under the curve (AUC). Variants of the sigmoid Emaxmodel were fit to the data from the three psychomotor performance tests. A triazolam dose of less than 0.5 mg was administered to seven of eight subjects in the TRZPROG and five of eight subjects in the TRZ group, resulting in lower triazolam AUC values for the TRZPROG than for the TRZ group (p = 0.0275). There was clear evidence for a pharmacodynamic interaction. Mean effect ratios for all tests were greater in the TRZPROG group than in the TRZ group (DSST, p = 0.0097; continuous performance test, p = 0.0338; hand-eye coordination, p = 0.0041). The TRZPROG group had lower EC50values than the TRZ group (DSST, p = 0.0435; continuous performance test, p = 0.0381; hand-eye coordination, p = 0.0154). These results confirm our hypothesis that the concurrent administration of progesterone enhances the effects of triazolam. This is new evidence that documents the effect of progesterone on pharmacodynamic response to benzodiazepines in humans. This study provides evidence that in vitro receptor binding observations qualitatively predict pharmacodynamic response to benzodiazepines. (J Clin Psychopharmacol 1995;15:3-11).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Forty-four patients with DSM-III-R generalized anxiety disorder participated in this double-blind, randomized study. Patients were on a benzodiazepine before the study and were stabilized on 3 to 5 mg/day lorazepam for 5 weeks (weeks 0 to 5). Thereafter, they were randomized to 15 mg/day buspirone or placebo for the following 6 weeks (weeks 6 to 11). During the first 2 weeks of double-blind, randomized treatment (weeks 6 to 7), lorazepam was tapered off. During weeks 12 to 13, patients received single-blind placebo. Assessment included the Hamilton Rating Scale for Anxiety, the State-Trait Anxiety Inventory, the Zung and Eddy Self-Rating Scale of Anxiety Symptoms, the Hamilton Rating Scale for Depression, and the Rome Depression Inventory, completed at weeks 0, 5, 6, 7, 8, 9, 11, and 13. Side effects were assessed through the Dosage Treatment Emergent Symptoms at the same times. The benzodiazepine-withdrawal syndrome was evaluated through a 27-symptom checklist (Clinical-Rated Benzodiazepine Withdrawal Symptom Schedule) at weeks 0, 5, 6, 7, 11, and 13. The results showed that buspirone was more effective than placebo and comparable to lorazepam. Buspirone-treated patients showed no rebound anxiety or benzodiazepine-withdrawal syndrome compared with placebo. Buspirone caused fewer side effects than lorazepam and was not different from placebo in this respect. Finally, buspirone maintained its anxiolytic effect for at least 2 weeks after the discontinuation of treatment. (J Clin Psychopharmacol 1995;15:12-19).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The purpose of this study was to assess the anxiolytic effect of MDL 11,939, a selective 5-HT20.05). The incidence of adverse events between treatments was similar. MDL 11,939 was well tolerated but did not demonstrate significant anxiolytic effects in this pilot study. (J Clin Psychopharmacol 1995;15:20-22).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Clinical data and uncontrolled observations have suggested that fluoxetine is helpful in some patients with borderline personality disorder.This article describes the results of a 13-week double-blind study of volunteer subjects with mild to moderately severe borderline personality disorder. Thirteen fluoxetine recipients and nine placebo recipients received treatment. Pretreatment and posttreatment measures were obtained for global mood and functioning, anger, and depression. The most striking finding from this study was a clinically and statistically significant decrease in anger among the fluoxetine recipients. This decrease was independent of changes in depression. These data support previous observations that fluoxetine may reduce anger in patients with borderline personality disorder. The number of subjects in this study was small, the placebo responsiveness was high, and the clinical characteristics of the patients were in the mild to moderate range of severity. The data cannot be extrapolated to more severely ill borderline patients, but further study of fluoxetine and other selective serotonin reuptake inhibitors is indicated in this population. (J Clin Psychopharmacol 1995;15:23-29).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The acute and subchronic effects of two dosages of a new serotonergic antidepressant, nefazodone, and those of the tricyclic imipramine were examined in a double-blind, crossover, placebo-controlled study. Twenty-four healthy subjects from two age groups (12 adults and 12 elderly from both sexes) received the four treatments (nefazodone, 100 and 200 mg twice daily; imipramine, 50 mg twice daily; and placebo) for 7 days with a 7-day washout period. Measurements were performed after the morning doses on day 1 and day 7. These included a standard over-the-road highway driving test, a psychomotor test battery, and sleep latency tests. Blood samples were taken on both days and analyzed to determine concentrations of parent drugs and their major metabolites. The main results showed that the reference drug, imipramine, had a detrimental effect after a single dose on lateral position control in the driving test, primarily in the adult group, that diminished after repeated dosing. Minor impairment on psychomotor test performance was found with both days. On the other hand, a single administration of both doses of nefazodone did not impair highway driving performance (even showed some improvement) and had no or only minor effects on psychomotor performance. After repeated dosing, nefazodone 200 mg twice daily (but not the 100-mg dose) produced slight impairment of lateral position control; dose-related impairment of cognitive and memory functions was found. The effects of nefazodone were generally in the same direction in both age groups. Significant correlations were found between steady-state concentrations of nefazodone in plasma (200-mg, twice-daily condition) as well as imipramine, and reaction time changes in a memory scanning task. Neither drug appeared to induce daytime sleepiness as measured by the sleep latency tests. (J Clin Psychopharmacol 1995;15:30-40).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The combination of classic monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressant drugs (TCAs) has been associated with a variety of adverse events.A switch in treatment from TCAs to moclobemide, a reversible and selective inhibitor of MAO-A, was investigated in a double-blind, placebo-controlled study in healthy volunteers. Two groups of 12 subjects were treated with either amitriptyline (75 mg/day) or clomipramine (100 mg/day) until steady-state conditions had been attained (14 days). Treatment with the TCAs was discontinued abruptly and switched to either a therapeutic dose regimen of moclobemide (300 mg/day) or placebo. The tolerability and safety pattern did not reveal any clinically relevant differences between moclobemide and placebo recipients, nor was there any sign of a pharmacokinetic interaction between the TCAs and moclobemide. In conclusion, the findings of this study suggest that therapeutic doses of moclobemide up to 300 mg daily can be given 24 hours after the last dose of treatment with either amitriptyline or clomipramine without major risks. (J Clin Psychopharmacol 1995;15:41-48).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Opiates were used to treat major depression until the mid-1950s. The advent of opioids with mixed agonist-antagonist or partial agonist activity, with reduced dependence and abuse liabilities, has made possible the reevaluation of opioids for this indication. This is of potential importance for the population of depressed patients who are unresponsive to or intolerant of conventional antidepressant agents. Ten subjects with treatment-refractory, unipolar, nonpsychotic, major depression were treated with the opioid partial agonist buprenorphine in an open-label study. Three subjects were unable to tolerate more than two doses because of side effects including malaise, nausea, and dysphoria. The remaining seven completed 4 to 6 weeks of treatment and as a group showed clinically striking improvement in both subjective and objective measures of depression. Much of this improvement was observed by the end of 1 week of treatment and persisted throughout the trial. Four subjects achieved complete remission of symptoms by the end of the trial (Hamilton Rating Scale for Depression scores less or equal to 6), two were moderately improved, and one deteriorated. These findings suggest a possible role for buprenorphine in treating refractory depression. (J Clin Psychopharmacol 1994;15:49-57).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine. (J Clin Psychopharmacol 1995;15:58-62).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Western countries experienced a widespread cocaine epidemic during the 1980s, and the number of frequent users has not declined in this decade.A key factor in the development of this epidemic has been the introduction of "crack," an affordable form of cocaine that appears to be more addicting than the powder. Epidemiologic studies indicate a high incidence of polysubstance abuse among cocaine abusers and probable gender differences in patterns of abuse and response to treatment. An abstinence syndrome has been documented in outpatients after the acute cessation of cocaine; the symptoms perhaps depend on the presence of cues to evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine is a psychostimulant drug that possesses euphorigenic and reinforcing properties. The fact that various animal species self-administer cocaine through the intravenous route provides a reliable animal model for the study of the molecular mechanism of cocaine action and for the characterization of the anatomical substrates responsible for the rewarding properties of the drug. A multisynaptic, allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to play an important role. This pathway may also be part of the neuronal substrates that mediate the reinforcing properties of other classes of abused drugs and, perhaps, motivated behavior in general. Because of this potent reinforcing nature of cocaine in humans, the problem of designing effective therapy for its addiction has not been simply solved. Clinical treatments, guided by animal studies and designed for specific attack of symptoms of the abstinence syndrome, craving and anhedonia, have been tested. To date, only a few agents have proved effective in controlled trials (amantadine, bromocriptine, carbamazepine, and desipramine) and these have limitations of side effects or delayed onset of action. Agents that interact with specific subcomponents of the dopamine system or its connections offer promise for the development of successful agents to treat cocaine abuse and craving in humans. (J Clin Psychopharmacol 1995;15:63-78).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID