抑郁患者选择性5-羟色胺再摄取抑制剂治疗与周期性肢体运动综合征

目的:考察选择性5-羟色胺再摄取抑制剂(selective serotonin reuptake inhibitor,SSRI)与抑郁患者的周期性肢体运动综合征(periodic limb movement syndrome,PLMS)的关系。方法:本研究是病例回顾性分析,来自广东省精神卫生研究所的多导睡眠图(polysomnography,PSG)数据库(2006年11月-2009年11月)。选择了31例接受SSRI治疗的抑郁患者组(治疗组),并设定了2个对照组:27例未接受药物治疗抑郁患者组(未治疗组)和31例正常对照组。根据2007版美国睡眠研究会标准,判定了睡眠分期、睡眠相关事件和PLMS。结果:SSRI治疗组(13.7±2.6)比未治疗组(5.3±1.4)和正常对照组(4.1±1.1)的周期性肢体运动指数(periodic limb movement index,PLMI)更高(F=10.373,P0.001),而且治疗组的PLMS发生率(41.9%)明显高于其他两组(未治疗组:11.1%,正常对照组:6.5%,χ2=10.227,P0.001)。logistic回归显示的SSRI剂量越高(OR=1.107,1.036～1.184)、REM潜伏期越长(OR=1.289,1.176～1.413)和微觉醒越多(OR=1.483,1.219～1.748),接受SSRI的被治疗者就越容易出现PLMS。结论:选择性5-羟色胺再摄取抑制剂可能增加了抑郁患者出现周期性肢体运动综合征的风险,是一个值得临床学家重视的药源性副反应。     

Selective serotonin reuptake inhibitor effects on neural biomarkers of perinatal depression

Archives of Women's Mental Health - The effect of perinatal selective serotonin reuptake inhibitors (SSRIs) on brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B...     

A selective serotonin reuptake inhibitor reduces REM sleep in the homing pigeon

Avian and mammalian 'rapid eye movement' sleep (REM sleep) resemble each other in several aspects. However, the question of whether REM sleep has a shared evolutionary ancestry in birds and mammals has yet to be thoroughly explored. The brain regions and neurotransmitter systems involved in the generation of mammalian REM sleep are phylogenetically ancient, and are also found in extant birds and reptiles. Several pharmacological experiments in birds indicate that similar neural substrates are involved in the regulation of avian and mammalian sleep. However, because the drugs used in these studies generally resulted in non-specific sleep loss, the neurochemical regulation of avian REM sleep in particular remains uncertain. The selective serotonin reuptake inhibitor (SSRI) zimelidine is known to reduce REM sleep in mammals. If avian REM sleep is similarly regulated by serotonin, it would be expected that an acute dose of a SSRI should also reduce avian REM sleep. To investigate a putative role of serotonin in the regulation of avian REM sleep, changes in sleep electroencephalogram (EEG) and behavior were recorded in five pigeons (Columba livia) after the administration of an acute dose of zimelidine. Our results demonstrate that the effects of zimelidine on avian REM sleep are comparable to those observed in mammals, indicating that serotonin may serve a similar function in the control of avian and mammalian REM sleep.     

CB-1 receptors modulate the effect of the selective serotonin reuptake inhibitor, citalopram on extracellular serotonin levels in the rat prefrontal cortex

A large percentage of depressed individuals use drugs of abuse, like cannabis. This study investigates the impact of cannabis on the pharmacological effects of the antidepressant citalopram. Using microdialysis in the prefrontal cortex of rats we monitored serotonin levels before and after cannabinoid (WIN55,212-2 or rimonabant) and citalopram administration. Stimulating CB-1 decreased the effect of citalopram on increasing serotonin levels in the prefrontal cortex. Blocking CB-1 augmented this effect of citalopram. Although repeating these experiments in a chronical setting is recommended the present results might have implication for the clinical effects of citalopram.     

The pharmacogenetics of the selective serotonin reuptake inhibitors

Summary Citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are selective serotonin reuptake inhibitors (SSRIs), which are thought to act as antidepressants through their ability to inhibit presynaptic serotonin reuptake in the brain. The elimination of the SSRIs proceeds predominantly via oxidation catalyzed by cytochrome P450 in the liver. Paroxetine and fluoxetine are potent inhibitors of cytochrome P4502D6 and hence may cause serious interactions with drugs metabolized by this isozyme, notably tricyclic antidepressants, some neuroleptics, and some antiarrhythmics. Citalopram, fluvoxamine and sertraline do not share this property. Fluvoxamine is the only SSRI that is a potent inhibitor of cytochrome P4501A2 and hence causes serious pharmacokinetic interactions with amitriptyline, clomipramine, imipramine, theophylline, and presumably caffeine and other drugs which are metabolized by the isozyme. Citalopram and fluoxetine are administered as racemates, but practically nothing is known about the stereoselective metabolism of the two drugs. Citalopram is partially metabolized via the mephenytoin oxidation polymorphism, and paroxetine is partially metabolized via the sparteine/debrisoquine oxidation polymorphism. The pharmacogenetic differences in the oxidation of the SSRIs themselves are probably of no clinical relevance.Abbreviations CYP cytochrome P450 - EM extensive metabolizer - PM poor metabolizer - SSRI selective serotonin reuptake inhibitor     

Selective serotonin reuptake inhibitor treatment of early postnatal mice reverses their prenatal stress-induced brain dysfunction

Prenatal stress has long-lasting effects on cognitive function and on the hypothalamic-pituitary-adrenal response to stress. We previously reported that the serotonin concentration and synaptic density in the hippocampus were reduced following prenatal stress [Int J Dev Neurosci 16 (1998) 209]. Since serotonin plays a role in the formation and maintenance of synapses, we hypothesized that a neonatal reduction in hippocampal serotonin levels may lead to learning disabilities in prenatally stressed mice. To test this hypothesis, we treated prenatally stressed mice with a selective serotonin reuptake inhibitor in order to normalize their postnatal serotonin turnover levels. What we found was that the oral administration of a selective serotonin reuptake inhibitor to prenatally stressed mice during postnatal weeks 1-3 but not 6-8 normalized their corticosterone response to stress, serotonin turnover in the hippocampus, and density of dendritic spines and synapses in the hippocampal CA3 region. Concomitantly, such treatment partially restored their ability to learn spatial information.     

Reasons for quitting serotonin reuptake inhibitor therapy: paradoxical psychological side effects and patient satisfaction

BACKGROUND: The goal of this study was to document the existence of psychological side effects associated with serotonin reuptake inhibitors (SSRIs) taken for depression and to determine their relationship to patients' decisions to stop treatment, and attitudes toward taking SSRIs again. METHOD: We conducted 161 semi-structured telephone interviews of adults who had completed a course of treatment for depression with one of the SSRIs. We identified 29 categories of unwanted psychological effects and analyzed data in terms of responders and non-responders, the former split into those who would, and those who would not take the same drug again if depressed in the future ('take-again responders' and 'not-again responders', respectively). RESULTS: Psychological side effects were cited just as often as physical side effects as the primary reason for quitting SSRI treatment. Non-responders cited psychological side effects rather than non-response as the primary reason for quitting, and not-again responders cited physical more than psychological side effects. Not-again responders and non-responders did not differ in the number of side effects experienced, and non-responders experienced significantly more unwanted psychological effects than either type of responder (chi2= 6.767, p=0.009). CONCLUSION: Psychological side effects might well be included in measures and discussions of side effects, even though they present no known physical danger to the patient.     

Progressive resistance to a selective serotonin reuptake inhibitor but not to cognitive therapy in the treatment of major depression

Recent research suggests that there may be a reduction in therapeutic response after multiple administrations of antidepressant drug (AD) therapy in patients with major depressive disorder. This study assessed the response to AD therapy and cognitive therapy (CT) of patients with a history of prior AD exposures. A sample of 240 patients with moderate-to-severe major depressive disorder entered a randomized controlled trial comparing pharmacotherapy with paroxetine to CT. Treatment was administered for 16 weeks. History of prior AD exposure was assessed with structured interviews, self-report, and medical records. Analyses were conducted using hierarchical linear models on the intent-to-treat sample. After controlling for various demographic and clinical factors, more prior AD exposures predicted poor response to paroxetine therapy but not to CT, as measured by the Hamilton Rating Scale for Depression (Hamilton, 1960; Williams, 1988). Whereas CT outcome was not significantly related to the number of prior AD exposures, a higher number of prior AD exposures was significantly associated with a lower response to paroxetine. If these findings are replicated in methodologically rigorous studies of paroxetine and other antidepressants, CT should be recommended, in preference to AD, for patients with multiple prior AD exposures.     

Prescribing selective serotonin reuptake inhibitors in older age

Apart from commercial reasons, two motivations have led to the introduction of SSRIs to replace the first and second generation antidepressants already available. One was the search for a more rational treatment, based on specific mechanisms, the other the development of effective treatments with fewer side effects, particularly for older patients, who have a greater sensitivity to cardio-vascular and central nervous system effects. The first has been frustrated up to a point, in that SSRIs and other single mechanism drugs do not appear to be more effective than the earliest relatively non-specific antidepressants. The second has been fulfilled, in that SSRIs generally are better tolerated in older patients and in overdose. However, there is a spectrum of other side effects that are particularly relevant in older age and that need attention when treating depression in this particular patient group.     

The safety of selective serotonin reuptake inhibitors: hemostasis

The literature data of the reaction of haemostatic system to antidepressants from the group of selective inhibitors of serotonin reuptake are summarized. The development of haemorrhagic complications is analyzed. The risk/benefit ratio is estimated for the treatment of depression in patients with acute myocardial infarction and stroke. A differential approach to indication of antidepressants is substantiated for the treatment of comorbid depressive disorders in different types of somatic pathology.     

Depression impairs learning,whereas the selective serotonin reuptake inhibitor,paroxetine, impairs generalization in patients with major depressive disorder

To better understand how medication status and task demands affect cognition in major depressive disorder (MDD), we evaluated medication-naïve patients with MDD, medicated patients with MDD receiving the selective serotonin reuptake inhibitors (SSRI) paroxetine, and healthy controls. All three groups were administered a computer-based cognitive task with two phases, an initial phase in which a sequence is learned through reward-based feedback (which our prior studies suggest is striatal-dependent), followed by a generalization phase that involves a change in the context where learned rules are to be applied (which our prior studies suggest is hippocampal-region dependent). Medication-naïve MDD patients were slow to learn the initial sequence but were normal on subsequent generalization of that learning. In contrast, medicated patients learned the initial sequence normally, but were impaired at the generalization phase. We argue that these data suggest (i) an MDD-related impairment in striatal-dependent sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced impairment in hippocampal-dependent generalization of past learning to novel contexts, not otherwise seen in the medication-naïve MDD group. Thus, SSRIs might have a beneficial effect on striatal function required for sequence learning, but a detrimental effect on the hippocampus and other medial temporal lobe structures is critical for generalization.     

Decreased reuptake of serotonin in human platelets after surgery.

We have documented earlier a decrease in platelet serotonin and a concurrent increase in plasma serotonin, 5-hydroxytryptamin (5-HT) after various forms of stress, suggesting a disturbed platelet 5-HT reuptake mechanism following stress. In order to further elucidate these findings, we have studied platelet 5-HT reuptake kinetics (Vmax and Km) in nine patients before and 4 days after major, uncomplicated abdominal surgery. We found a significant decrease in the maximal 5-HT reuptake velocity (Vmax) after surgery and changes in Km, verifying alterations in the affinity of the platelet 5-HT transport system. The present results thus confirm the hypothesis that 5-HT reuptake kinetics are altered following adrenergic hyperactivity. A decrease in platelet 5-HT reuptake may bear implications for our understanding of poststress adaptive changes in the cardiovascular system as well as in the central nervous system (CNS) serotonergic neurones following stressful stimulation.     

Contribution of serotonin reuptake to differential histamine and serotonin secretion from rat peritoneal mast cells

Inflammation Research -     

Treatment with selective serotonin reuptake inhibitors for enhancing wound healing

Selective serotonin reuptake inhibitors (SSRIs) are well-established medications for the treatment of mood disorders including major depression. These agents are also known to exhibit potent antiplatelet and endothelium protective effects effects. Additionally, SSRIs can exacerbate the development of inflammation, and modulate the interleukin and interferon production. All of the above suggest that SSRIs therapy could be considered as a potential strategy for the wound healing treatment. We summarized some body of the available data on the history of serotonin metabolism, mechanism of action of ketanserin, and hypothesize why SSRIs may be beneficial in the wound repair natural history. Different pathophysiological considerations are also reflected in this review. Finally, we suggest that the topical use of SSRIs may represent a promising avenue for future strategies affecting wound repair in high-risk patients, especially those with diabetes mellitus, venous insufficiency, obesity, and other vascular disorders.     

Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine

Objective

The aim of the present study was to compare the effects on serum cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor, and kamishoyosan, a Japanese traditional medicine, in midlife women with psychological symptoms.

Methods

Seventy-six women with psychological symptoms such as anxiety and mild depression as menopausal symptoms were enrolled in this study. Thirty-eight women received oral administration of 10 mg paroxetine every day, and 38 women received oral administration of kamshoyosan every day for 6 months. Overall climacteric symptoms were assessed using Greene's climacteric scale. Serum levels of cytokines were measured using a multiplexed human cytokine assay.

Results

Greene's total scores in both women treated with paroxetine and in women treated with kamishoyosan decreased significantly. Percentage decreases in Greene's total, psychological and vasomotor scores during the 6-month period in the paroxetine group were significantly greater than those in the kamishoyosan group. Serum IL-6 concentration in women treated with paroxetine decreased significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory protein (MIP)-1β and monocyte chemoattractant protein-1 in women treated with paroxetine decreased significantly. On the other hand, serum IL-6 concentration in women treated with kamishoyosan decreased significantly, but other serum concentrations did not change significantly.

Conclusion

Decrease in IL-6 concentration may be involved in the mechanism of the actions of both paroxetine and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be useful as a marker of treatment. The action of paroxetine may also be associated with decreases in IL-8, IL-10, MIP-1β.