阿立哌唑辅助氟伏沙明治疗强迫障碍的临床观察

目的：探讨阿立哌唑辅助氟伏沙明治疗强迫障碍的临床疗效及安全性。方法：将54例强迫障碍患者随机分为两组（各27例）：阿立哌唑（2．5—10mg／d）辅助氟伏沙明（250—300mg/d）组（研究组）、氟伏沙明（250～300mg／d）组（对照组）,治疗观察期均为8周。两组患者于基线及治疗2、4、6、8周末分别评定Yale—Brown强迫量表（Y—BOCS）,并采用副反应量表（TESS）评定治疗期间的不良反应。结果：研究组、对照组分别脱落1例、2例。研究组的强迫思维和强迫行为评分在基线及2、4、6、8周末时点间比较差异均有统计学意义（P〈0．05）;2周末时,两组间的强迫思维评分比较差异有统计学意义（P〈0．05）,而强迫行为评分比较差异无统计学意义（P〉0．05）;4周末时,两组间的强迫行为评分比较差异有统计学意义（P〈0．05）;8周末时,两组间强迫症状有效率比较差异有统计学意义（P〈0．05）,而不良反应发生率比较差异均无统计学意义（P〉0．05）。结论：阿立哌唑辅助氟伏沙明可有效、持续地改善强迫障碍患者的强迫症状,且不良反应发生率与单一氟伏沙明治疗相当。     

氟伏沙明与氯米帕明治疗强迫症的疗效观察

目的探讨氟伏沙明与氯米帕明治疗强迫症的疗效和不良反应。方法将84例强迫症患者随机分为观察组（氟伏沙明治疗）42例,对照组（氯米帕明治疗）42例,共治疗8周,于治疗前及2、4、6、8周末采用Yale—Brown强迫量表（Y—BOCS）评价其疗效,治疗中采用不良反应量表（TESS）评价其不良反应。结果两组治疗前Y—BOCS评分差异无显著性（P〉0．05）;从治疗第2周末开始两组Y-BOCS评分均较前有显著下降（P〈0．01）,同期组间比较差异无显著性（P〉0．05）：治疗8周末观察组有效率69．05％,对照组有效率66．67％,两组差异无显著性（P〉0．05）;治疗组不良反应较对照组少且轻。结论氟伏沙明治疗强迫症,疗效显著,不良反应少,依从性好,是一种安全有效的短期治疗强迫症的理想药物。     

氟伏沙明与氯米帕明治疗强迫症的疗效观察

目的探讨氟伏沙明与氯米帕明治疗强迫症的疗效和不良反应。方法将84例强迫症患者随机分为观察组(氟伏沙明治疗)42例,对照组(氯米帕明治疗)42例,共治疗8周,于治疗前及2、4、6、8周末采用Yale-Brown强迫量表(Y-BOCS)评价其疗效,治疗中采用不良反应量表(TESS)评价其不良反应。结果两组治疗前Y-BOCS评分差异无显著性(P>0.05);从治疗第2周末开始两组Y-BOCS评分均较前有显著下降(P<0.01),同期组间比较差异无显著性(P>0.05);治疗8周末观察组有效率69.05%,对照组有效率66.67%,两组差异无显著性(P>0.05);治疗组不良反应较对照组少且轻。结论氟伏沙明治疗强迫症,疗效显著,不良反应少,依从性好,是一种安全有效的短期治疗强迫症的理想药物。     

Effect of fluvoxamine on platelet 5-HT2A receptors as studied by [3H]lysergic acid diethylamide ([3H]LSD) binding in healthy volunteers

Alterations in platelet 5-HT_2A receptor characteristics have been reported in major depression as well as in other psychiatric diseases, and some effort has been made to utilize platelet 5-HT_2A receptor status as a biological correlate to antidepressant drug response. In order to investigate whether treatment with a selective serotonin reuptake inhibitor affects platelet 5-HT_2A receptors, we have studied platelet [³H]lysergic acid diethylamide ([³H]LSD) binding in healthy subjects treated with fluvoxamine in increasing dosage once weekly for 4 weeks. After 1 week of fluvoxamine treatment (25 mg/day), both B_max and K_d were significantly lower than before the start of the treatment (19.9 versus 25.5 fmol/mg protein, P = 0.005 for B_max; 0.45 versus 0.93 nM, P = 0.006 for K_d). B_max returned to baseline during week 2, whereas K_d was lower than the baseline value throughout the treatment period. After discontinuation of fluvoxamine treatment, there was a significant increase in K_d (0.50 nM before discontinuation vs. 1.14 nM after discontinuation; P = 0.001), but not in B_max. The study demonstrates that fluvoxamine affects platelet 5-HT_2A receptor status irrespective of underlying psychiatric disease, and that this effect is evident already after 1 week at a subtherapeutic fluvoxamine dose. Received: 11 October 1996/Final version: 12 March 1997     

Non-competitive inhibition of clomipramineN-demethylation by fluvoxamine

The selective serotonin reuptake inhibitor fluvoxamine interferes with the metabolism of tricyclic antidepressants. The present investigation was set out to characterize these interactions in vitro using rat liver microsomes and in vivo by analysing levels of clomipramine and metabolites in sera of depressed patients treated concomitantly with fluvoxamine and clomipramine. Clomipramine wasN-demethylated and hydroxylated in vitro by microsomes toN-desmethylclomipramine, 8-hydroxyclomipramine, and 10-hydroxyclomipramine. Kinetic analyses revealed K_m values of 6.2 µM forN-demethylation and 1.2 µM for 8-hydroxylation. Fluvoxamine was a non-competitive inhibitor forN-demethylation with mean K_i value of 6 µM. In the sera of patients treated with daily doses of 150 mg clomipramine and varying doses of fluvoxamine, decrease in the formation ofN-desmethylclomipramine and 8-hydroxyclomipramine were found in comparison to those in sera of patients receiving clomipramine as monotherapy. Taken together, the data give evidence that fluvoxamine is a potent non-competitive inhibitor ofN-demethylation and to a minor extent of 8-hydroxylation of clomipramine. Because of the species differences in the metabolism of xenobiotics between rodents and humans, conclusions from animal studies on the clinical situation must be drawn cautiously. Nevertheless, the in vitro approach was helpful to understand drug interactions between clomipramine and fluvoxamine in psychiatric patients.     

Repeated treatment with antidepressant drugs induces subsensitivity to the excitatory effect of 5-HT4 receptor activation in the rat hippocampus

The effect of repeated treatment with various antidepressant drugs on the reactivity of CA1 neurons to the 5-HT₄ receptor agonist zacopride was examined. Zacopride decreased the calcium-activated afterhyperpolarization and adaptation, it also elicited a slow membrane depolarization associated with an increase in input resistance. All those effects may have contributed to the zacopride-induced increase in the amplitude of population spikes, evoked in the CA1 cell layer by stimulation of the Schaffer collateral/commissural pathway. The later effect of zacopride was concentration-dependent and was antagonized by the 5-HT₄ receptor antagonist DAU 62805. Repeated (14 days, twice daily), but not single, administration of the antidepressant drugs imipramine, citalopram, fluvoxamine and paroxetine (10 mg/kg) attenuated the effect of zacopride on population spikes. Because inhibitory 5-HT_1A and excitatory 5-HT₄ receptors are colocalized on pyramidal neurons, and our previous data demonstrated an increase in the 5-HT_1A receptor-mediated inhibition after repeated treatment with antidepressants, we conclude that treatment with antidepressant drugs may enhance the inhibitory effect of 5-HT directly, by increasing the 5-HT_1A receptor responsiveness, and indirectly, by inducing subsensitivity to the 5-HT₄ receptor activation. Received: 24 June 1996 / Accepted: 28 August 1996     

Fluvoxamine augmentation in chronic schizophrenia: An open exploratory study

The effect of augmenting standard antipsychotic treatment with the specific serotonergic reuptake inhibitor (SSRI) fluvoxamine was examined in severely disabled chronic schizophrenic inpatients using an open, naturalistic protocol. Fluvoxamine in doses ranging from 25 to 200 mg was added to the antipsychotic medication which was kept constant. Patients were followed for the duration of treatment (to date up to 7·5 months). Assessment included BPRS SANS SAPS and CGI scales (CGI only in the most severely disturbed), and global impressions of occupational and social functioning. Fourteen (74%) of the 19 patients studied showed improvement using 15 per cent change in SANS score or CGI improvement score > = 1 as criterion. The symptom constellation appeared to influence the rate and timing of response. Ten patients experienced exacerbations, some within 2 months of starting treatment, others after 5–6 months. The findings suggest that SSRI augmentation may be effective in severely disabled schizophrenics.     

A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression

Deborah Roth, Jeffrey Mattes, K. Harnett Sheehan and David V. Sheehan: A Double-Blind Comparison of Fluvoxamine, Desipramine and Placebo in Outpatients with Depression. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 929–939.

1. 1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder.

2. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated.

3. 3. Studies of major depression ought to be designed to last 8–10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.

Effects of anxiolytic and antidepressant drugs on long-lasting behavioural deficits resulting from one short stress experience in male rats

Exposure of male Wistar rats to one single session of ten inescapable footshocks induces changes in the behavioural responses to environmental stimuli as measured in the noise test 14 days later. Shocked (S) rats showed decreased locomotion and rearing during the first 3 min of exposure to a novel environment compared to control (C) rats. When the 85 dB background noise was switched off a marked immobility response emerged in S rats, concomitant with a further decrease in locomotion and rearing. In response to noise off, C rats showed hardly any immobility and a much smaller reduction in locomotion and rearing compared to S rats. These long-lasting changes in behaviour were not reversed by acute treatment with the antidepressants fluvoxamine (3.0–30.0 mg/kg) and desmethylimipramine (DMI, 2.5–10.0 mg/kg) injected IP 30 min before the noise test on day 14 following the shock session. Chronic treatment (day 1 to day 14) with flvoxamine or DMI did not reverse the behavioural deficits induced by shock exposure. Diazepam (0.6–5.0 mg/kg) administered acutely only reversed the effects of shock on locomotion during the first 3 min of the noise test. Chronic treatment with diazepam normalized the shock-induced decrease in locomotion and attenuated the rearing decrease during the first 3 min of the test, and partially restored shock-induced changes in behavioural response to switching off the noise. The most potent drug in this study was the 5-HT_1A receptor agonist flesinoxan (0.3–3.0 mg/kg). Both acute and chronic drug treatment were equally effective in reversing the shock-induced locomotion deficits as well as the marked immobility response in S rats, although rearing was not reversed. However, flesinoxan also increased locomotion and reduced rearing in C rats, suggesting some nonspecific stimulating effects of flesinoxan. In conclusion, the footshock-induced long-lasting behavioural changes are sensitive to treatment with (putative) anxiolytic agents, whereas no beneficial effect of the antidepressant drugs was found.     

氟伏沙明合并舒必利治疗抑郁症分析

目的 探讨氟伏沙明合并舒必利治疗抑郁症的临床疗效及安全性.方法 将87例符合务件的抑郁症患者随机分为氟伏沙明联合舒必利组(观察组)及单用氟伏沙明组(对照组),疗程8周.用4级临床疗效、汉密尔顿抑郁量表(HAMD)、简明精神病量表(BPRS)观察疗效,用副反应量表(TESS)评定不良反应.结果 治疗8周后2组BPRS、HAMD总分及因子分都较治疗前明显降低,差异有统计学意义(P=0.009);氟伏沙明联合舒必利组痊愈率显著高于单用氟伏沙明,差异有统计学意义(x2=43.85,P＜0.05);观察组BPRS的思维障碍、激活性、敌对猜疑因子分和总分治疗8周后明显低于对照组,差异有统计学意义(t=3.48,5.32,4.21,6.75;P＜0.05);观察组HAMD的睡眠障碍和总分明显低于对照组,差异有统计学意义(t=11.32,7.75;P＜0.01).结论 氟伏沙明联合小剂量舒必利治疗抑郁症疗效优于单用氟伏沙明,不良反应少.