Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people

This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen.     

Serotonin reuptake inhibitors reverse the impairments in behaviour,neurotransmitter and immune functions in the olfactory bulbectomized rat

This experiment investigated the effects of chronic treatment with serotonin reuptake inhibitors, fluvoxamine (10 mg/kg, i.p.) and sertraline (10 mg/kg, i.p.), for 20 days on the behaviour, neurotransmitter concentrations and immune functions in the olfactory bulbectomized (OB) rat model of depression. Following fluvoxamine and sertraline administration, the hyperactive behaviour of the OB rat in the ‘open field’ was significantly attenuated. In the elevated plus-maze, an increase in the number of entries into the open arms and a decrease in the time spent on the closed arms were also largely reversed in the OB rat after fluvoxamine and sertraline treatment. Fluvoxamine and sertraline treatments reversed the decrease in the brain concentrations of noradrenaline (NA) of the OB rat and the increase in the 5-hydroxyindole-3-acetic acid (5-HIAA) concentration. Fluvoxamine and sertraline treatment also significantly reversed the suppression of lymphocyte proliferation in the OB rat. However, only the chronic administration of fluvoxamine significantly improved depressed neutrophil phagocytosis, sertraline being without effect on this immune parameter.     

A Review of 19 Double-Blind Placebo-Controlled Studies in Social Anxiety Disorder (Social Phobia)

Summary: Nineteen double-blind placebo-controlled studies on the treatment of Social Anxiety Disorder (Social Phobia) are reviewed. Initial trials yielded a high degree of efficacy for phenelzine, a large difference between drug and placebo and a low rate of placebo response. Controlled studies with RIMAs (moclobemide and brofaromine) yielded more moderate levels of efficacy and more pronounced placebo effects. Results of the Liebowitz Social Anxiety Scale (LSAS) permit a comparison of the outcomes of the different controlled trials. Overall, the reduction in the mean total score with various drugs is inferior to 50%, probably because the chronic nature of the disorder is not amenable to drastic changes in short-term trials. Results with the LSAS and other scales justify a ranking of the efficacy of the drugs: Classical MAOIs > SRIs > RIMAs. Two controlled studies with benzodiazepines (clonazepam and bromazepam) would position them together with the SRIs relative to efficacy but with problems associated with unwanted effects and dependence. Controlled studies with SRIs (paroxetine and fluvoxamine) demonstrated very significant differences from placebo. Paroxetine is the SRI most extensively studied in Social Anxiety Disorder with positive therapeutic results.     

Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation

Aims Inhibition of cytochrome P450 (CYP) activity by selective serotonin reuptake inhibitors (SSRIs) has frequently been reported with regard to pathways mediated by CYP2D6, CYP3A4/5, and CYP1A2. Little data exist on the capability of SSRIs to inhibit CYP2C9.
Methods We investigated the effect of SSRIs on p -hydroxylation of phenytoin (PPH), an established index reaction reflecting CYP2C9 activity, in an in vitro assay using liver tissue from six different human donors.
Results In control incubations (without inhibitor), 5-( p -hydroxy-phenyl)-5phenylhydantoin (HPPH) formation rates were: V _max 0.023  nmol min⁻¹  mg⁻¹; K _m 14.3  &mgr;m. Average inhibition constants ( K _i ) differed significantly among the SSRIs, with fluvoxamine having the lowest K _i (6  &mgr;m ) followed by R-fluoxetine (13  &mgr;m ), norfluoxetine (17  &mgr;m ), RS-fluoxetine (19  &mgr;m ), sertraline (33  &mgr;m ), paroxetine (35  &mgr;m ), S-fluoxetine (62  &mgr;m ), and desmethylsertraline (66  &mgr;m ). Thus, assuming comparable molar concentrations at the site of inhibition, fluvoxamine can be expected to have the highest probability of interfering with the metabolism of CYP2C9 substrates. S-fluoxetine is on average a 5 fold weaker CYP2C9 inhibitor than either R-fluoxetine or the racemic mixture.
Conclusions These findings are consistent with published case reports describing SSRI-related increments in plasma phenytoin levels. Because phenytoin has a narrow therapeutic index, plasma levels should be closely monitored when SSRIs are coadministered.     

Enhanced long-term synaptic depression in an animal model of depression.

BACKGROUND: A growing body of evidence suggests a disturbance of brain plasticity in major depression. In contrast to hippocampal neurogenesis, much less is known about the role of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) regulate the strength of synaptic transmission and the formation of new synapses in many neural networks. Therefore, we examined the modulation of synaptic plasticity in the chronic mild stress animal model of depression. METHODS: Adult rats were exposed to mild and unpredictable stressors for 3 weeks. Thereafter, long-term synaptic plasticity was examined in the hippocampal CA1 region by whole-cell patch clamp measurements in brain slices. Neurogenesis was assessed by doublecortin immunostaining. RESULTS: Exposure to chronic mild stress facilitated LTD and had no effect on LTP. Chronic application of the antidepressant fluvoxamine during the stress protocol prevented the facilitation of LTD and increased the extent of LTP induction. Neurogenesis in the dentate gyrus was impaired after chronic stress. CONCLUSIONS: In addition to neurogenesis, long-term synaptic plasticity is an important and ubiquitous form of brain plasticity that is disturbed in an animal model of depression. Facilitated depression of synaptic transmission might impair function and structure of brain circuits involved in the pathophysiology of major depression. Antidepressants might counteract these alterations.     

氟伏沙明联合阿立哌唑治疗强迫症对照研究

目的 探讨氟伏沙明联合阿立哌唑治疗强迫症的临床疗效和安全性.方法 将55例强迫症患者随机分为两组,均口服氟伏沙明治疗,观察组联合阿立哌唑治疗.观察6个月.于治疗前后采用Yale-Brown强迫量表评定临床疗效,副反应量表评定不良反应.结果 治疗后两组Yale-Brown强迫量表评分均较治疗前持续下降（P＜0.01）,观察组治疗各时段评分均显著低于对照组（P＜0.05或0.01）.治疗6个月观察组显效率、总有效率均高于对照组.两组不良反应均轻微,治疗各时段副反应量表评分及不良反应发生率比较差异均无显著性（P＞0.05）.结论 氟伏沙明联合阿立哌唑能增强抗强迫效应,治疗强迫症起效快,疗效显著,安全性高,依从性好,优于单用氟伏沙明治疗.     

认知行为疗法、氟伏沙明联合氯米帕明治疗青少年强迫症效果观察

正强迫症(obsessive compulsive disorder,OCD)是精神科和心理科常见的一种神经症性障碍,以无法控制的强迫观念和强迫行为为特征。Heyman等流行病学调查发现,超过50%的成人强迫症起病于18岁以前,群体患病率约1%~4%~([1])。临床实践表明,认知行为疗法(cognitive behavioral therapy,CBT)、选择     

Obsessive–compulsive disorder and spectrum across the life span

An obsessive–compulsive disorder (OCD) spectrum has been proposed, which includes a group of disorders that share certain features with OCD including clinical symptoms (repetitive behaviours and thoughts), neurobiology (e.g. neurotransmitters) and preferential response to anti-obsessional treatments, such as the selective serotonin reuptake inhibitors (SSRIs). Three distinct clusters have been identified within the OCD spectrum, i.e. disorders concerning preoccupations with bodily sensations or appearance, impulsive disorders, and neurologically based disorders, and these share phenotypic features. Using one example from each of these clusters, body dysmorphic disorder (BDD), pathological gambling (PG) and autism, respectively, the phenomenology, neurobiology and pharmacotherapy indicates that specific biological factors are shared by OCD and by these disorders and correlate with the severity of repetitive behaviours. Thus, in common with OCDs, in BDD there is increased activity in the limbic regions; in PG there is evidence of deficiencies in 5-HT function and receptors; and in autism there are restricted interests and repetitive behaviours which may be influenced by serotonergic mechanisms. Our findings support the notion that targeted treatments, for example using SSRIs, for the behaviours associated with these disorders are effective. Our review considers one SSRI treatment in particular, fluvoxamine, and conclusions should be drawn in light of this. Further testing of our hypothesis would be prudent to confirm its validity.     

丁螺环酮对难治性强迫症治疗的增效作用

目的：比较氟伏沙明合并丁螺环酮与氟伏沙明治疗难治性强迫症的疗效。方法：将符合条件的60例难治性强迫症患者随机分成两组,分别给与氟伏沙明合并丁螺环酮（合用组）和氟伏沙明（对照组）,进行12周的系统治疗,使用Yale—Brown强迫量表（Y—BOCS）,汉密尔顿焦虑量表（HAMA）评估其疗效;以治疗中出现的症状量表（TESS）和有关的实验室检查评定不良反应。结果：治疗以后丽组患者的Y-BOCS评分均明显下降,合用组的治疗效果较好,两组之间差异存在显著性（P〈0．01）,并且合用组起效快;而两组HAMA量表的评分明显下降,合用组的治疗效果较好,两组之间差异存在显著性（P〈0．01）,合用组起效快;合用组的不良反应发生率高于对照组,但差异无显著性;两组药物引起的不良反应均为轻度或中度,表现有所不同,患者耐受性好。结论：氟伏沙明合并丁螺环酮治疗难治性强迫症的疗效优于单独使用氟伏沙明组,且合用组起效较快,不良反应较轻。