ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Research into the psychobiology of premenstrual dysphoric disorder (PDD) finds alterations in markers associated with serotonergic neurotransmission.Supporting this is work showing that patients with PDD respond to some agents that block the reuptake of serotonin. In this open trial, patients were treated for one cycle with placebo and then for three consecutive cycles with the serotonin reuptake inhibitor paroxetine. The study population was composed of 14 participants who met DSM-IV criteria for PDD with moderate to severe symptomatology and specifically endorsed anger and irritability as a central premenstrual complaint. Patients showed modest improvement over the course of the pretreatment evaluation, with significant improvement occurring for feelings of worthlessness, decreased interest, and low energy. The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001). A group of items from daily ratings indicative of anger and irritability (mood swings, anger and irritability, behavioral dyscontrol, and interpersonal conflicts) also showed improvement (F[1,13] = 5.94; p < 0.03). Various definitions of response were applied to treatment completers. The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3). These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD. (J Clin Psychopharmacol 1996;16:3-8).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In a double-blind, placebo-controlled study of 72 patients with bulimia nervosa treated successfully with inpatient psychotherapy, the efficacy of fluvoxamine in maintaining improvement was tested. Fluvoxamine and placebo, respectively, were given over a period of about 15 weeks (2-3 weeks inpatient titration phase, 12 weeks outpatient relapse-prevention [maintenance] phase). The variables assessed concerned bulimic behavior and other aspects of eating disorders, global status, depression, anxieties, obsessive-compulsive behavior, and other aspects of psychopathology. Because the dropout rate was relatively high (N = 27 [33%]) and because it was considerably higher in the fluvoxamine group (19 out of 37 subjects), analyses were performed on the intent-to-treat sample (ideally including all 72 subjects). Results of the completer sample analyses (including only those subjects who finished the study) are briefly presented for comparison.In both the intent-to-treat and the completer analyses, the following scales showed fluvoxamine to have a significant effect in reducing the return of bulimic behavior: (1) self-ratings: Eating Disorder Inventory (EDI)-bulimia, urges to binge in previous week and the number of actual binges in the previous week; (2) expert ratings: Psychiatric Status Rating Scales for Bulimia nervosa, Structured Interview for Anorexia and Bulimia nervosa (SIAB)-"total score," SIAB-subscale "fasting," and SIAB-subscale "vomiting." Two further variables (EDI-total score and SIAB-subscale "bulimia") showed the superior relapse prevention effects of fluvoxamine compared with placebo for the completer sample, while they did not reach significance for group-by-time interactions in the intent-to-treat sample. During a final, short (4-week) off-medication phase, no effect of the discontinuation of medication was observed. (J Clin Psychopharmacol 1996;16:9-18).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

65 years) men and women (N = 12 each) were compared with those in healthy younger (18-40 years) men and women (N = 12 each). All subjects were classified as extensive metabolizers of dextromethorphan (cytochrome P4502D6). Subjects were administered a 300-mg dose of nefazodone hydrochloride for the evaluation of S-D pharmacokinetics. For the evaluation of S-S pharmacokinetics, 300-mg doses of NEF were administered twice daily (every 12 hours) for 8 days (single morning dose on day 8). Serial blood samples were collected after the single dose and the morning dose on day 8 of the twice-daily administration; a blood sample for trough level was collected from each subject just before the morning dose on days 2 to 8 of the twice-daily dosing to assess the attainment of steady state. Plasma samples were assayed for NEF, HO-NEF, and mCPP by a specific, validated high-performance liquid chromatography assay. After a single dose of NEF, the mean peak concentrations in plasma and the area under the curves (AUC) for NEF and HO-NEF were about twofold higher in elderly versus young subjects, but mean AUCs for mCPP were similar. Levels in plasma for NEF, HO-NEF, and mCPP reached steady state by day 3 of multiple dosing. At steady state, exposure to NEF and HO-NEF, based on AUC(TAU) values, was quite variable among age/gender groups but on the average was about 50% higher in elderly women compared with the other three groups of subjects; the exposure to mCPP at steady state was similar in elderly and young subjects. Because all subjects were extensive metabolizers, the effect of gender or age on the pharmacokinetics of NEF and its metabolites in poor metabolizers is not known. There were no serious or unexpected adverse experiences observed in this study. Assuming that similar systemic exposure to NEF and its active metabolites will result in similar therapeutic effects in young and elderly individuals, the difference in systematic exposure to NEF and HO-NEF in elderly subjects suggests that NEF treatment should be initiated at half the usual dose with titration upward and that the usual precautions exercised in treating elderly patients should be used. (J Clin Psychopharmacol 1996;16:19-25).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

A double-blind, placebo-controlled study using 12 healthy men was designed to evaluate pharmacokinetic and pharmacodynamic interactions when nefazodone and haloperidol are coadministered. Two groups of six subjects each received a 5-mg oral dose of haloperidol or a placebo on study days 1 and 2. Nefazodone, 200 mg, was administered to all 12 subjects twice daily (every 12 hours) on study days 3 to 9; on study day 10, only the morning dose of nefazodone was administered. On study days 9 and 10, all subjects also received 5 mg of haloperidol or a placebo along with the morning dose of nefazodone. Serial blood samples for pharmacokinetic analysis were collected from each subject over a 12-hour period after the morning dose on study days 1, 2, 9, and 10. Plasma samples were assayed for haloperidol, reduced haloperidol, nefazodone, hydroxynefazodone and m-chlorophenylpiperazine by specific, validated high-performance liquid chromatogoraphy methods. Psychomotor performance tests to evaluate haloperidol pharmacodynamics were also performed on days 1, 2, 9, and 10. Reduced haloperidol in the majority of samples was below the limit of quantitation; therefore, the effect of nefazodone on the pharmacokinetics of reduced haloperidol could not be determined. The administration of 5 mg of haloperidol to subjects dosed with nefazadone to steady state led to a modest pharmacokinetic interaction, as indicated by a 36, 13, and 37% increase in mean area under the curve (AUCO0-12), highest concentration, and 12-h concentration values for haloperidol, respectively; only the increase in AUC was statistically significant. In contrast, the steady-state pharmacokinetics of nefazodone, hydroxynefazodone, and m-chlorophenylpiperazine were not affected by the administration of haloperidol. Although there were significant differences observed in some psychomotor performance tests, the effects of nefazodone on the pharmacodynamics of haloperidol could not be consistently demonstrated. The results from this study suggest that nefazodone has only modest pharmacokinetic and pharmacodynamic interactions with haloperidol. Although no specific recommendations can be made, dosage adjustment may be necessary for haloperidol when coadministered with nefazodone. (J Clin Psychopharmacol 1996;16:26-34).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Low doses of cisapride (5-10 mg twice daily) produced relatively rapid relief from nausea elicited by venlafaxine in six patients with treatment-refractory recurrent major depression. This further suggests that the nausea associated with serotonergic reuptake inhibition may be a result of 5-hydroxytryptamine (5-HT3) agonist action. No adverse cardiac experiences were encountered in spite of the potential interaction of cisapride with selective serotonin reuptake inhibitors at the cytochrome P4503A4 enzyme system. (J Clin Psychopharmacol 1996;16:35-37).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p <0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients. (J Clin Psychopharmacol 1996;16:38-44).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Because of large interindividual variabilities in the pharmocokinetics of haloperidol (HPDL), empirically adjusting the dose to achieve steady-state levels in plasma (Css) is a time-consuming process. We report a method to individualize dose to achieve a desired C (ss25 ng/ml) Cssrange of HPDL. On day 1 of the study, each patient received an oral "test" dose of HPDL (15 mg), and blood was drawn 24 hours later to determine drug levels in plasma (C (24h)). The first 34 patients (group I) were then maintained empirically on 2, 5 to 8, or 10 to 15 mg twice daily of oral HPDL concentrate for 5 days to achieve a low, medium, or high Cssrange, respectively. For the next 58 patients (group II), the dose of HPDL to achieve the assigned Cssrange was computed by using C24hin a prediction formula. Application of the C24hcorrectly predicted the maintenance dose required to achieve the Cssin 73.2% of the cases. Further, there was a highly significant correlation (R2= 0.877, p < 0.0001) between the predicted dose and the actual dose required to achieve the targeted Cssrange. On the basis of these results, we have formulated a nomogram to help predict the maintenance dose required to achieve low, medium, or high HPDL targeted ranges at various C24hvalues. (J Clin Psychopharmacol 1996:16:45-50).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

This study aimed to evaluate the concurrent and lifetime psychiatric comorbidity and drug use patterns in patients admitted to the hospital for detoxification from benzodiazepines.Psychiatric assessments using the Structured Clinical Interview for DSM-III-R with a psychosis screening module (SCID-P and II) were conducted in 30 inpatients admitted to the medical unit treatment unit of the Clinical Research and Treatment Institute of the Addiction Research Foundation for the treatment of severe benzodiazepine dependence. Patients (mean age, 36 years; range, 22-58; number of DSM-III-R criteria met for benzodiazepine substance dependence, greater or equal to 7 out of 9 [73%], all 9 criteria [40%]) used benzodiazepines and other drugs over prolonged periods of time at high doses, and their daily functioning was substantially impaired (Mean Global Assessment of Functioning Score, 48; range, 31-60). The most common lifetime psychiatric diagnoses were major depression (33%), other psychoactive drug dependence (100%) (opioids, 77%; alcohol, 53%), and panic disorder (30%). Current psychiatric diagnoses in addition to benzodiazepine dependence included other psychoactive substance use disorders (83%) (opioids, 67%; cocaine, 13%; multiple concurrent substance use, 17%), panic disorder (13%), and generalized anxiety disorder, (20%). Personality disorders included antisocial (42%), avoidant (25%), and borderline (17%). These findings demonstrate that in patients severely dependent on benzodiazepines, additional psychoactive substance use and mental disorders are prominent. The pattern of drug use and psychiatric comorbidity differentiates these patients from therapeutic-dose benzodiazepine users. (J Clin Psychopharmacol 1996;16:51-57).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharmacotherapy, treatment during the clinical trial included individual counseling, weekly group therapy, and on-site medical services. Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning, as assessed by the Addiction Severity Index, rates of urinalysis tests positive for opioids, and self-reports of opioid withdrawal symptoms, illicit opioid use, and cocaine use. Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed, and improvements for both groups were large and occurred rapidly after treatment entry. A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group. These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone. In addition, these results demonstrate the benefits of drug abuse treatment, both for drug and alcohol use and in other areas of psychosocial functioning. (J Clin Psychopharmacol 1996;16:58-67).

ISSN:0271-0749    

出版商:OVID    

年代:1996

数据来源: OVID