The platelet of the patients with ischemic cardiopathy and cardiac valve disease showed a reduction of 8OH-DPAT binding sites

Depression is prospectively associated with increased risk of coronary artery disease in individuals initially free of clinical cardiovascular disease probably by an increased platelet activity. The serotonergic receptors mainly implied in depression are 5-HT1A and 5-HT2 receptors. Activation of 5HT2 receptor induces platelet aggregation. Drugs with 5-HT1A receptor agonist and 5-HT2A receptor antagonist effects reduced the receptor-mediated platelet aggregation. There are only indirect data about 5-HT1A receptors presence in platelet membranes, thus our aims were to study the characteristics of the platelet membranes 5-HT1A binding sites of both healthy volunteers and patients with cardiac valve disease and ischemic cardiopathy. The bound of the 5-HT1A selective agonist 3H-8OH-DPAT to the platelet membranes 5-HT1A binding sites of patients with cardiac valve disease and ischemic cardiopathy were compared with a control group of healthy voluntaries using radioligand binding methods. The patients with cardiovascular disease showed a reduction (-50.40%) (p<0.01) of the 3H-8OH-DPAT bound to the platelet membranes 5-HT1A receptors (1.652+/-0.79 fmol/mg protein) with respect to the control group (3.331+/-0.16 fmol/mg protein). 3H-8OH-DPAT binding to human platelet membranes is saturable, of high affinity, and seems selective for 5-HT1A receptors, and similar to that described in animal brain and in other human cells. Patients with ischemic cardiopathy and cardiac valve disease showed a reduction of the 8OH-DPAT bound to the platelet membranes. Taken together, these findings suggest that the 8OH-DPAT bound to the human platelet membranes is modulated by modifications produced by cardiovascular disease conditions.     

Depressive disorders and the menopause transition

Aim

Depressive disorders and symptoms are common among middle-aged women. The effects of hormones on depression remain unclear. This review aims to clarify the nature of depressive disorders during the menopause transition as well as their links with climacteric syndrome, sexuality, cardiovascular risk and cognitive function.

Material and methods

The recent literature on depressive disorders and menopause is reviewed.

Results and conclusions

Women are more vulnerable than men to depressive disorders. Endocrine influences have been postulated but differences in, for example, coping style and response to stress may also contribute to the gender difference in the prevalence of depressive disorders. Gender differences in socialization may lead to higher rates of depression in women. There are data top suggest that menopause and depression are associated, although there is not a common clear causative factor. Women with climacteric symptoms (hot flushes, night sweats, vaginal dryness and dyspareunia) are more likely to report anxiety and/or depressive symptoms. Bothersome vasomotor symptoms could be associated with sleep disturbances, which in turn can increase reports of anxiety and depressive symptoms. Biopsychosocial and partner factors have a significant influence on middle-aged women's sexuality and depressive disorders, and most antidepressants can have a negative effect on sexual response. Lastly, studies have consistently shown that women with high levels of depressive symptoms are at greater cardiovascular risk and have poorer cognitive function than non-depressed women. At present, a direct relationship between psychiatric symptoms and hormonal changes such as estrogen decrease has not been clearly found. Stress, educational level, ethnicity, socioeconomic factors and partner status may influence the prevalence and clinical course of both menopause symptoms and depressive disorders. Since in many cases depression is a lifelong condition, and is associated with severe comorbid conditions, further studies are needed to improve the early diagnosis of depression; it may be advisable to monitor a woman's mental health during the menopause transition to prevent a depressive disorder having long-term negative consequences.     

Effects of a putative antidepressant with a rapid onset of action in defeated mice with different coping strategies

There is evidence suggesting that stressful social events may result in depressive-like disorders, but the development of these disorders depend on the way in which people cope with stress. Although antidepressants are useful their drawback is a delay in the therapeutic effects, moreover not all the patients show an adequate response to this treatment. The aim of this study was to analyse the effect of RS 67333, which is a 5-HT(4) receptor partial agonist and a putative antidepressant which exhibits a rapid onset of action and to determine whether this drug reverses the behavioural and physiological effects that are generated by chronic defeat in subjects who manifest a more vulnerable profile in their response to stress. Male mice were exposed to defeat for 21 consecutive days using a sensorial contact model. After 18 days of defeat, 2 groups of subjects were established, active and passive, in accordance with the behaviour that was manifested during social confrontation, and drug treatment was initiated for 5 days. Finally, the animals were subjected to a forced swimming test (FST). The results revealed higher corticosterone levels in passive mice after the last defeat. Additionally, 3 days after the last defeat, they showed lower corticosterone levels and higher splenic IL-6 and TNF-α levels and hypothalamic GR mRNA levels when compared to their active and manipulated control counterparts. Passive mice had higher 5-HT(1A) receptor mRNA levels than the manipulated controls and a lower MR/GR ratio than active mice. Similar to stress, the drug increased hypothalamic GR mRNA levels, but it did not affect other measured physiological variables or social behaviour, which suggested that the mechanism of this drug is not the most adequate for reversing stress-induced effects in this model. Nevertheless, the treatment increased swimming and decreased immobility in the FST, suggesting an antidepressant potential for this drug.     

Long-Term Side Effects of Newer-Generation Antidepressants: SSRIS, Venlafaxine, Nefazodone, Bupropion, and Mirtazapine

Anecdotal reports have suggested that the long-term use of selective serotonin reuptake inhibitors (SSRIs) may be associated with significant weight gain, sexual dysfunction, drug interactions, and discontinuation symptoms. Are these effects inevitable or can they be managed effectively with the appropriate interventions? In reviewing published, controlled clinical trials, it has been noted that many depressed patients experience weight gain during remission with or without treatment. Most antidepressants appear to produce a 3- to 4-kg weight gain after 6–12 months of therapy, which may be managed with nutritional counseling and exercise. The exception is mirtazapine, which appears to be associated with significant weight gain early in therapy. Antidepressant-induced sexual dysfunction is also common but may be managed with the addition of an antidote or substitution. Drug interactions are most common with fluvoxamine, nefazodone, and fluoxetine because these agents are more likely to affect the metabolism of commonly prescribed medications. It may be possible to prevent discontinuation symptoms with a cross taper to another antidepressant or by slowly tapering the antidepressant.     

选择性5-HT再摄取抑制剂与5-HT、NE再摄取双重抑制剂治疗围绝经期情绪障碍疗效

目的观察选择性5-HT再摄取抑制剂(SSRIs)与5-HT、NE再摄取双重抑制剂(SNRIs)治疗围绝经期情绪障碍的临床疗效。方法选择我院门诊就诊的围绝经期情绪障碍患者40例作为入组对象,随机分为SSRIs组和SNRIs组,疗程12周,自入组、治疗2、4、6、8、12周使用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)对两组患者症状进行组间、组内比较。结果与入组的比较治疗2、4、6、8、12周两组患者的情绪障碍均得到持续改善:SSRIs组HAMD躯体症状(t=2.05,2.82,3.28,6.60,10.34;P0.05或0.01),心境症状(t=2.03,2.14,3.38,5.05,8.96;P0.05或0.01);SSRIs组HAMA躯体症状(t=2.12,2.47,3.31,6.21,8.86;P0.05或0.01),心境症状(t=2.03,2.38,3.38,6.24,7.08;P0.05或0.01),SNRIs组HAMD躯体症状(t=3.92,4.68,5.67,7.22,10.94;P0.01),心境症状(t=3.55,5.42,7.41,9.14,12.31;P0.01),SNRIs组HAMA躯体症状(t=4.42,5.57,7.00,10.43,13.06;P0.01),心境症状(t=2.81,3.12,5.32,6.86,23.40;P0.01);治疗各周SNRI组HAMD躯体症状(t=2.76,2.71,2.44,6.15,18.00;P0.05或0.01),心境症状(t=2.06,2.15,3.14,5.35,7.22,10.75;P0.05或0.01),HAMA躯体症状(t=3.04,3.63,4.70,4.28,9.26;P0.01),心境症状(t=2.81,3.12,5.32,6.86,23.40;P0.01)改善程度明显优于SSRI治疗组。结论 SSRIs与SNRIs药物均能显著改善围绝经期患者的情绪障碍,两者比较SNRIs药物整体疗效明显优于SSRIs药物。     

Relevance of seminal plasma nitric oxide levels and the efficacy of SSRI treatment on lifelong premature ejaculation

The aim of this study was to determine the relevance of seminal plasma nitric oxide (NO) levels and the efficacy of selective serotonin reuptake inhibitor (SSRI) treatment on premature ejaculation. A total of 16 men (aged 32.18 ± 3.32) with lifelong premature ejaculation [intravaginal ejaculation latency time (IELT) <1 min] and 11 healthy men (control group) were included in this study. The healthy men formed Group 1, and the patients were randomly categorised into two groups. Group 2 patients received 20 mg day^?1 of paroxetine, and Group 3 patients received 50 mg day^?1 of sertraline for 4 weeks. Baseline and post‐treatment findings were compared among the three groups. Mean baseline seminal NO levels in men with premature ejaculation were significantly higher than in the healthy control group (32.24 ± 5.61 μm  l^?1 versus 19.71 ± 3.50 μm  l^?1, respectively) (P < 0.001). There was no significant difference between the sertraline and paroxetine groups in terms of IIEF scores, IELT scores and NO levels. At the end of the first month, the mean IELT scores of the paroxetine and sertraline groups showed a significant improvement compared with the baseline values (P < 0.001). After treatment with paroxetine and sertraline, NO levels dec‐reased from baseline. Our study indicates that premature ejaculation is significantly related with a higher level of seminal NO. Baseline seminal plasma NO values obtained in patients with premature ejaculation were significantly higher than in the healthy control group. After treatment with SSRIs, decreased seminal NO may retard ejaculation. Further studies are needed to confirm this suggestion and the role of NO in the pathophysiology and treatment of premature ejaculation.     

文拉法辛缓释剂与SSRTs治疗难治性抑郁症对照研究

目的探讨文拉法辛缓释剂治疗难治性抑郁症的临床疗效及安全性。方法将60例难治性抑郁症患者随机分为两组各30例，分别给予文拉法辛缓释剂和SSRTs抗抑郁剂治疗，疗程12mo。于治疗前及治疗1mo、3mo、6mo、12mo末采用汉密顿抑郁量表评定临床疗效，副反应量表评定不良反应，生存质量量表评定生存质量。结果汉密顿抑郁量表评分两组治疗1mo末起均较治疗前有显著或极显著下降（P〈0．05或0．01），两组间同期评分比较，研究组较对照组下降更显著（P〈0．05）。生存质量量表评分两组治疗1mo末起均较治疗前有显著或极显著升高（P〈0．05或0．01），两组间同期评分比较，研究组心理领域、社会关系、环境因素因子分较对照组升高更显著（P〈0．05或0．01）。两组不良反应均较轻微，除口干、多汗、便秘发生率两组有显著性差异（x^2=4．94，3．92，5．12，P〈0．05）外，余差异无显著性。结论文拉法辛缓释剂治疗难治性抑郁症疗效较SSRTs显著，且能显著改善患者的生存质量，安全性高，依从性好。     

Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram,fluoxetine, fluvoxamine and paroxetine

Objectives: The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. Methods: The study was carried out as an in vivo single-dose study including 24 young, healthy men. All volunteers had been identified as sparteine- and mephenytoin-extensive metabolisers. The volunteers received in randomised order, at weekly intervals, increasing single oral doses of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6), mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals because of the long half-life of fluoxetine and its metabolite norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg and fluvoxamine was given in doses of 25, 50, 100 and 200 mg. Results: With increasing doses, there was a statistically significant increase in the sparteine metabolic ratio (MR) (P < 0.01, Page’s test for trend) for all four SSRIs. The increase was modest after intake of citalopram and fluvoxamine, while the increase was more pronounced after fluoxetine intake, although no volunteers changed phenotype from extensive metabolisers to poor metabolisers. Three of the six volunteers changed phenotype from extensive metabolisers to poor metabolisers after intake of 40 or 80 mg paroxetine. There was a statistically significant increase in the mephenytoin S/R ratio (P < 0.01, Page’s test for trend) with increasing doses of fluoxetine and fluvoxamine, but not after citalopram and paroxetine. However, no volunteers changed phenotype from extensive to poor metabolisers of S-mephenytoin. After intake of fluvoxamine, the urinary excretion of the metabolites related to N3 demethylation of caffeine were below the limit of quantification, whereas there were no significant changes in the urinary caffeine metabolic ratios after intake of the other three SSRIs. Conclusion: This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account. Received: 11 December 1995/Accepted in revised form: 29 February 1996     

The Management of Anxiety and Depressive Disorders: A Review

While anxiety and mild-moderate depression (the so-called neuroses) are the commonest mental disorders, they receive scant attention. They should be considered together, because they commonly occur together, are typically chronic, and respond to the same treatment. This review challenges traditional notions about the neuroses, by examining the reasons for their co-morbidity, the effectiveness of SSRIs in anxiety, and the biological basis of anxiety. From neuro-endocrine, psycho-immunology, genetic and clinical studies, anxiety and depression could denote manifestations of an underlying cause. Anxiety results from a dysregulation of homeostasis in the serotonin and noradrenergic systems, which SSRIs stabilize. Treatment guidelines recommend that SSRIs and SNRI should be first-line in the treatment of anxiety disorders, in combination with psychotherapy, with benzodiazepines used on short-term basis. Remission should be the goal of treatment. Outcome should include clinical, functional and disability assessments, graded in terms of response, remission and recovery. Perhaps the SSRIs and SNRI should be recognized as anti-neurotic. Mental disorders probably exist in a biological system with serotonin at the root of the neuroses, while dopamine sub-stands the psychoses.