氟伏沙明联合认知行为疗法治疗儿童青少年强迫症对照研究

目的 探讨氟伏沙明联合认知行为疗法治疗儿童青少年强迫症的临床疗效和安全性.方法 将60例儿童青少年强迫症患者随机分为两组,每组30例,两组均口服氟伏沙明治疗,研究组在此基础上联合认知行为治疗,观察12周.于治疗前及治疗2周、4周、8周、12周末采用Yale-Brown强迫量表评定临床疗效,儿童大体评定量表评定儿童精神障...     

Tolerability and safety of fluvoxamine and other antidepressants

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.     

Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure

AIMS

To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine.

METHODS

A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h.

RESULTS

With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 ± 19 vs. 15 ± 9 ng ml⁻¹; difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration–time curve was almost three times higher [885 ± 560 vs. 304 ± 84 ng h ml⁻¹; difference (95% CI) 581 (205, 957), P < 0.05]; half-life was prolonged by 63% [21.1 ± 6.2 vs. 12.9 ± 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 ± 0.77 vs. 2.25 ± 0.66 l h⁻¹ kg⁻¹; difference (95% CI) −1.13 (−1.80, −0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=−0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects.

CONCLUSIONS

Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF.     

LC-S／MS法测定人血浆中氟伏沙明浓度及其人体生物等效性

目的建立测定人血浆中氟伏沙明浓度的方法,对国产和进口马来酸氟伏沙明片进行生物等效性研究。方法24名健康男性志愿者按2×2交叉试验方案设计,分别口服受试制剂和参比制剂各50mg,并在给药后96h内动态采集血样,采用LC-MS／MS法测定血浆中氟伏沙明浓度,计算药动学参数,评价两种制剂的生物等效性。结果受试制剂和参比制剂的主要药动学参数‰分别为（18．79±8．15）μg·L^-1和（19．04±7．49）μg·L^-1,t。分别为（3．734±0.90）h和（3．814±1．02）h,AI‰分别为（327．574±131．93）μg·h·L^-1和（349．364±159．63）μg·L^-1,AUC0→∞分别为（346．95±134．84）μg·L^-1和（368．27±163．59）μg·h·L^-1,t1／2分别为（14．554±3．14）h和（14．15±3．17）h,两制剂主要药动学参数经对数转换后进行方差分析及双单侧t检验,并计算90％置信区间,表明两种制剂生物等效,受试制荆相对于参比制剂的生物利用度为（97．08±16．70）％。结论本方法可用于氟伏沙明人体药动学及生物等效性研究,统计分析证实马来酸氟伏沙明国产与进口制剂生物等效。     

Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder

Aims: The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode. Methods: A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables. Results: Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI. Conclusion: Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.     

氨磺必利联合氟伏沙明治疗强迫症患者临床疗效观察及安全性

目的：探讨氨磺必利联合氟伏沙明治疗强迫症患者临床疗效观察及安全性。方法：哪的95例强迫症患者,按照随机表法分为观察组49例与对照组46例。观察组采用氨磺必利联合氟伏沙明治疗,对照组采用氟伏沙明治疗。两组疗程均为12周。比较两组治疗疗效,治疗前后Yale-Browm强迫量表评分、汉密尔顿抑郁量表(HAMD)24项和汉密尔顿焦虑量表(HAMA)14项评分变化,及药物副反应发生情况。结果：观察组治疗总有效率(81.63%)高于对照组(63.04%),且有统计学差异(P<0.05)。两组治疗后强迫行为、强迫思维和总分较治疗前降低(观察组：t=39.823、23.416、56.832,对照组：t=24.299、17.259、28.681,P<0.05);观察组治疗后强迫行为、强迫思维和总分低于对照组(t=24.922、8.756、19.574,P<0.05)。两组治疗后HAMD和HAMA评分较治疗前降低(观察组：t=18.551、21.163,对照组：t=15.649、16.199,P<0.05);观察组治疗后HAMD和HAMA评分低于对照组(t=8.927、9.363,P<0.05)。两组药物副反应发生率比较无统计学差异(P>0.05)。结论：氨磺必利联合氟伏沙明治疗强迫症患者临床疗效明显,且用药安全性良好,值得临床借鉴。     

氟伏沙明与氯米帕明治疗强迫症的对照研究

目的比较氟伏沙明与氯米帕明治疗强迫症的疗效和不良反应。方法强迫症患者共64例，根据入组序号随机分为2组，疗程8周。应用恐怖／强迫量表（MSCPOR）、汉密尔顿焦虑量表（HAMA）评定疗效，TESS评价不良反应。结果氟伏沙明组治疗总有效率90．6％。氯米帕明组治疗总有效率84．3％，与氟伏沙明组相比差异无统计学意义（P〉0．05）。氟伏沙明治疗过程中出现药物不良反应较氯米帕明轻。结论氟伏沙明是一种治疗强迫症安全有效的药物。