ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability.The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed. (J Clin Psychopharmacol 1997;17:247-254).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The safety and efficacy of brofaromine, a reversible and selective monoamine oxidase inhibitor, were examined in a multicenter trial of 102 outpatients with social phobia.After a 1-week placebo washout, subjects were randomly assigned to 10 weeks of treatment with either brofaromine (N = 52) or placebo (N = 50). Brofaromine dosage began at 50 mg/day and was titrated to a maximum of 150 mg/day, depending on treatment response. Brofaromine produced a significantly greater change from baseline in Liebowitz Social Anxiety Scale (LSAS) scores compared with placebo, F(1) = 6.01, p < 0.016. Mean LSAS scores decreased from 81.8 at baseline to 62.6 at endpoint for brofaromine, t = 5.41, p < 0.001, and from 79.8 to 70.7 for placebo, t = 3.66, p < 0.001. Eleven of the 14 brofaromine early terminators discontinued because of adverse experiences, as did 4 of the 17 placebo early terminators. Side effects more common with brofaromine than placebo included insomnia, dizziness, dry mouth, anorexia, tinnitus, and tremor. No clinically significant variations in vital signs or laboratory values were found. The findings are consistent with the clinical efficacy for the treatment of social phobia. (J Clin Psychopharmacol 1997;17:255-260).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Serotonergic antidepressants have been shown to be effective treatments for premenstrual dysphoric disorder (PMDD).The efficacy of nonserotonergic antidepressants is less well studied. This study was a two-center, parallel design, placebo-controlled, randomized trial of fluoxetine, bupropion, and placebo in women with PMDD. Thirty-four women with PMDD completed 1 month of single-blind placebo and 2 months of fluoxetine 20 mg/day (N = 10), bupropion 100 mg three times daily (N = 12), or placebo (N = 12). Clinical Global Impressions (CGI) Scale, an expanded form of the Hamilton Rating Scale for Depression (HAM-D), and Global Assessment Scale (GAS) ratings were obtained premenstrually in each of the three treatment cycles. The three treatment groups differed significantly in efficacy by CGI ratings. Fluoxetine was superior to both bupropion and placebo. Comparison of posttreatment to pretreatment HAM and GAS scores demonstrated significant superior efficacy of fluoxetine compared with placebo. Posttreatment HAM and GAS scores for bupropion were intermediate between but not significantly different from fluoxetine or placebo. In summary, fluoxetine was significantly superior to bupropion and placebo as an effective treatment for PMDD. Although some improvement with bupropion was noted, and both medications were well tolerated, patient satisfaction was far greater with fluoxetine. (J Clin Psychopharmacol 1997;17:261-266).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Obsessive-compulsive disorder (OCD) has been successfully treated with proserotonergic agents for some years. Clomipramine was the first drug used, but several clinical trials have been conducted more recently to assess the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to compare the antiobsessional efficacy of three SSRIs, fluvoxamine, paroxetine, and citalopram. Thirty obsessive-compulsive patients without co-morbid axis I diagnoses except for tic disorder as assessed by DSM-III-R criteria gave informed consent and were recruited consecutively; they underwent a 10-week randomized treatment with fluvoxamine, paroxetine, or citalopram. Ratings were performed under blind conditions every 2 weeks from baseline to the end of the study and by the Yale-Brown Obsessive-Compulsive Scale, the National Institute of Mental Health-Obsessive-Compulsive Scale, the Clinical Global Impressions Scale, and the Hamilton Rating Scale for Depression. Quantitative and qualitative analyses of the antiobsessional efficacy of the three drugs were completed with analysis of variance with repeated measures and survival analysis. The results showed no significant differences between the three treatments. The preliminary conclusions drawn from this study concern the interchangeable antiobsessional effects of different SSRIs, although further studies of "cross-response" to these drugs are needed. (J Clin Psychopharmacol 1997;17:267-271)

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This randomized, double-blind clinical trial involving 198 generalized anxiety disorder (GAD) patients was conducted to more clearly define gepirone's role for the treatment of anxiety in daily dosages of 10 to 45 mg compared with diazepam and placebo. A secondary goal was to test for possible discontinuation symptoms after abrupt discontinuation of therapy. After a 1-week washout period, patients were treated for 8 weeks and then abruptly shifted under single-blind conditions for 2 weeks on placebo. The highest attrition rate occurred with patients on gepirone (58%) and the lowest on diazepam (34%). Medication intake for week 4 was 19.5 +/- 12.5 mg/day diazepam and 19.0 +/- 11.5 mg/day gepirone and was similar at week 8. The major adverse events were light-headedness, nausea, and insomnia for gepirone and drowsiness and fatigue for diazepam. Clinical improvement data showed gepirone's anxiolytic response to be delayed, being significant from placebo beginning at week 6, whereas diazepam caused significantly more relief than placebo from week 1 onward. Taper results showed that only diazepam, but not gepirone, caused a temporary worsening of anxiety symptoms or rebound. (J Clin Psychopharmacol 1997;17:272-277)

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The present study examined the efficacy of fluvoxamine in the treatment of trichotillomania (TM) and coexistent clinical features.Twenty-one participants with a principal diagnosis of TM were given fluvoxamine in a 12-week open trial. For 13 patients who completed treatment, significant improvement was noted on only a few measures of hair pulling. End-state analyses for the entire group of participants, however, demonstrated significant improvement in measures of distress, duration, control, and resistance. Significant decreases over treatment were also found on measures of coexistent anxiety for both the completer and the entire participant groups; depressive symptoms improved for completers. Conclusions about the effectiveness of fluvoxamine for treatment of TM cannot be drawn, given the uncontrolled nature of the study; however, end-state analyses suggest the potential utility of fluvoxamine in a subset of patients with TM. (J Clin Psychopharmacol 1997;17:278-283).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline.The pharmacokinetics of desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+ 358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+ 44%) with sertraline; the mean desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng [center dot] h/mL (+ 421%) with paroxetine versus from 611 to 838 ng [center dot] h/mL (+ 37%) with sertraline; and the mean desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+ 511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+ 19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmaxand AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the desipramine concentration changes. Thus, when coadministered with 50 mg/day desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively. (J Clin Psychopharmacol 1997;17:284-291).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Hyperprolactinemia and hyponatremia are adverse drug reactions regularly reported for selective serotonin reuptake inhibitors.Results from animal studies suggest that serotonin receptors of different subtypes are involved in the mediation of these effects. We have investigated to what extent fluvoxamine alters serum prolactin and serum sodium levels and whether these effects are related to platelet 5-hydroxytryptamine 2A (5-HT (2A)) receptor status, as studied by [(3) H]lysergic acid diethylamide ([(3) H]LSD) binding. Eight healthy subjects were given fluvoxamine in increasing dosage from 25 mg/day to 200 mg/day during 4 weeks, and serum sodium and serum prolactin concentrations were obtained weekly. All subjects had normal prolactin and sodium levels before start of treatment. Two subjects had substantial increases in serum prolactin levels (up to 35 micro gram/L) during fluvoxamine treatment, and these two subjects had higher Bmaxfor platelet [(3) H]LSD binding before fluvoxamine treatment than the six other subjects (32.7 vs. 23.1 fmol/mg protein). There was a small, nonsignificant decrease (mean 1.0 mmol/L) in serum sodium levels after institution of fluvoxamine but a significant increase (mean 1.9 mmol/L) in serum sodium levels after discontinuation of the drug (p = 0.02). Bmaxfor [(3) H]LSD binding and change in serum sodium concentration after institution of fluvoxamine showed a significant positive correlation (r = 0.85; p = 0.007). The results indicate that fluvoxamine affects serum prolactin as well as serum sodium concentrations and lend indirect support to the suggestion that 5-HT2Areceptors might be involved in the mediation of these effects. (J Clin Psychopharmacol 1997;17:292-297).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The current study uses utility analysis to assess economic and quality-of-life benefits of risperidone in patients with chronic schizophrenia. A retrospective analysis was performed on Positive and Negative Syndrome Symptoms (PANSS) data obtained from the published Canadian multicenter risperidone trial (part of the North American trial). Cluster analysis applied to endpoint PANSS scores, including all patients (N = 135), identified three clusters representing 130 patients with mild, moderate, and severe symptomatology. A narrative health state profile was written for each cluster, and 100 psychiatric nurses from Washington, DC, were asked to assign preference ratings to each one using linear analog and standard gamble (SG) methods. Mean utility values (confidence interval 95%) obtained from the SG ratings for the three health state profiles were 0.61 +/- 0.069 (mild); 0.36 +/- 0.073 (moderate); and 0.29 +/- 0.071 (severe). The mild health state (including the majority of risperidone 6 mg-treated patients) was rated by nurses to have a 0.25 +/- 0.0501 greater utility than the moderate health state (composed of the majority of haloperidol-treated patients). The results of these utility evaluations (SG) by the nurses were related to the clinical outcome for three of the six drug treatment groups (N = 65) by multiplying the percentage of patients in each of the three clusters, both at baseline and endpoint, who were receiving risperidone 6 mg/day, haloperidol, or placebo, by the utility value for the health state assigned to that cluster. The gain in utility for risperidone-treated patients was 2.6 times higher (0.125) compared with haloperidol-treated patients (0.049), and 7 times higher compared with placebo (-0.021). After multiplying the gain in utility of each treatment by the remaining expected life span for men and women, it was found that risperidone-treated patients obtained more than twice as many quality-adjusted years as haloperidol patients. The incremental drug treatment cost divided by the incremental benefit of risperidone versus haloperidol was found to yield a favorable, generally accepted cost-utility ratio. (J Clin Psychopharmacol 1997;17:298-307).

ISSN:0271-0749    

出版商:OVID    

年代:1997

数据来源: OVID